Crimean-Congo Haemorrhagic Fever

Overview

Crimean-Congo haemorrhagic fever (CCHF) is a widespread tick-borne disease, endemic in Africa, the Balkans, the Middle East and Asian countries south of the 50th parallel north. It is a rapidly progressive febrile illness that leads to severe disease including haemorrhagic manifestations and death in a large proportion of cases.

Disease epidemiology

CCHF was first detected in 1944 in Crimea, among soldiers and agricultural workers.

The CCHF virus causes severe outbreaks, with a case fatality rate of 10–40%. It is estimated that around 10,000 and 15,000 human infections, including approximately 500 fatalities, occur globally per year.

Pathogen(s)

CCHF is caused by CCHF virus (CCHFV), a tick-borne virus. Ticks of the genus Hyalomma are the main vector of CCHFV. The virus infects a wide range of animals such as cattle, sheep and goats.

Transmission

CCHFV is transmitted to humans through:

• Bite of an infected tick 

• Contact with infectious body fluids (blood, urine, vomitus, faeces, secretions, semen, breast milk) and/or organs of infected persons. 

• Contact with infected animals or their tissues. 

• Contact with contaminated surfaces or materials (e.g., needles and contaminated medical equipment). 

Healthcare-associated transmission may occur during patient care, specimen collection, handling or laboratory processing, particularly through needlestick injuries, exposure to infectious blood or body fluids, improper cleaning or disinfection of medical equipment, reuse of needles, or contact with contaminated medical supplies. Appropriate infection prevention and control measures and laboratory biosafety precautions are essential to minimise these risks.

Incubation period: Typically 2 – 7 days; range of 1 – 14 days.

Infectious period: Cases are considered infectious from the onset of symptoms and for as long as the virus is present in their blood or other body fluids.

Clinical features

The clinical presentation of CCHF ranges from mild illness to severe haemorrhagic disease with multi-organ failure. Symptomatic illness typically progresses through three phases, although not all patients develop haemorrhagic manifestations.

Pre-haemorrhagic phase

Symptoms typically begin suddenly and may include:

• High fever

• Headache

• Myalgia

• Fatigue

• Neck pain and stiffness

• Sore eyes, photophobia

• Red eyes, flushed face

• Cough, sore throat

• Nausea, vomiting

• Diarrhoea, abdominal pain

• Confusion or agitation

Haemorrhagic phase

The haemorrhagic phase typically begins 3-5 days after symptom onset. Clinical signs during this phase may include:

• Petechial rash on the skin and internal mucosal surfaces such as the mouth and throat, including red spots on the roof of the mouth

• Ecchymoses (larger areas of bruising)

• Severe nosebleeds and uncontrolled bleeding at injection sites

• Generalised bleeding from the gums and orifices

• Intra-abdominal bleeding, intracranial bleeding

• Tachycardia, lymphadenopathy, jaundice and hepatomegaly

• Hypotension, kidney failure, sudden liver failure or pulmonary failure

• Neurological symptoms such as meningism and confusion

Convalescent phase

In fatal cases, death typically occurs between days 5 and 14 of illness, usually from haemorrhage, multi-organ failure or shock.

In non-fatal cases, the convalescent phase begins around 10 - 20 days after initial symptom onset. Most patients make a full recovery, though some may experience prolonged fatigue and malaise.

Risk factors

Risk factors include:

• Relevant travel to affected countries or regions with ongoing CCHF outbreak.

• Contact with confirmed or suspected cases, or their blood and body fluids.

• Contact with infected animals or animal products, including during slaughter or butchering.

• Contact with contaminated surfaces or materials (e.g., needles and contaminated medical equipment).

Diagnosis

Acute CCHF infection is diagnosed by detection of CCHFV RNA in blood specimens using reverse transcription polymerase chain reaction (RT-PCR).

For suspected CCHF cases, clinicians should consult CDA before arranging laboratory investigations. Laboratory investigations, including routine haematology and biochemistry testing, should not be performed at primary care facilities for suspect CCHF cases. Clinically indicated investigations should be undertaken at facilities with appropriate biosafety arrangements.

Specimens may be referred to the National Public Health Laboratory (NPHL) for CCHF testing. NPHL will provide guidance on specimen collection, packaging, transport and testing requirements.

Treatment and management

Supportive Care

Supportive care remains the mainstay of treatment and can improve chances of survival. Management should include:

• Close clinical and laboratory monitoring

• Careful fluid and electrolyte management

• Appropriate blood component replacement for clinically significant bleeding, cytopenias, or coagulopathy

• Maintenance of oxygenation and haemodynamic support

• Organ support such as renal replacement therapy or mechanical ventilation when indicated

Suspected secondary infections or co-infections should be evaluated for and treated on clinical grounds.

Antiviral Therapy

There is currently no approved antiviral treatment for CCHF. The antivirals (i.e., Ribavirin and Favipiravir) described below have been used or investigated in the context of CCHF, but their evidence base remains limited.

Ribavirin

Ribavirin has been used off label in the treatment of CCHF and may be beneficial if initiated early in the illness. However, evidence of its effectiveness remains limited, and the optimal dosing regimen and duration of treatment have not been established. Further research is needed to define its role in CCHF management. Wherever possible, patients receiving ribavirin should be enrolled in a randomised clinical trial to assess clinical outcomes and safety.

Favipiravir

Favipiravir has demonstrated antiviral activity against CCHF in preclinical studies, including animal models. However, evidence of its effectiveness in humans remains insufficient, and it is not currently an established treatment for CCHF.

Precaution, prevention, and control

General advice

All staff who come into direct contact with a suspected or confirmed CCHF case or their blood and body fluids, including (but not limited to) healthcare workers, persons responsible for transporting patients (e.g., ambulance staff), and cleaners, should implement appropriate infection prevention and wear enhanced personal protective equipment (PPE) comprising of:

• Disposable fluid-resistant hood to cover the head and neck areas (staff with long hair may wish to use head cover prior to wearing hood)

• Eye protection gear (e.g., disposable downward face shields secured at forehead or goggles)

• Fluid-repellent N95 mask

• Inner and outer disposable fluid-resistant (AAMI 4) gown (should extend to below knee)

• 12-inch double nitrile or latex gloves certified for healthcare use (extended cuffs should reach up to mid forearm)

• Disposable fluid resistant boot covers (should extend up to knee-height)

Patients who are under investigation for CCHF, pending transfer to the High-Level Isolation Unit (HLIU) at the National Centre for Infectious Diseases (NCID), should be isolated in an Airborne Infection Isolation Room (AIIR), at a minimum.

Only essential staff who have been pre-identified and trained in the donning and removal of PPE should attend to the patient. Staff attending to suspect CCHF disease cases should be closely monitored (e.g., twice daily temperature monitoring), even if they wear the appropriate PPE. Entry of non-essential staff to the patient’s room should be restricted. A register of all staff who enter the patient’s room should be maintained. Visitors should not be allowed.

Waste generated from suspected and/or confirmed cases should be double-bagged, sealed and disposed of as biohazardous waste by a licensed biohazard waste contractor. Environmental surfaces should be cleaned and disinfected using 5,000 ppm sodium hypochlorite. Disinfectants should be applied (not sprayed) before cleaning. Surfaces contaminated with blood, other body fluids, secretions, excretions or spills should be disinfected using 10,000 ppm sodium hypochlorite after the spill has been removed using solidifiers or absorbent powder.

Persons with skin or mucosal exposure to blood or body fluids from a suspected and/or confirmed case should immediately wash affected skin surfaces with soap and water. Mucous membranes (e.g., conjunctiva) should be irrigated with copious amounts of water or eyewash solution. Exposed persons should immediately seek advice from infectious diseases physician and report the exposure to CDA.

CDA will conduct contact tracing for contacts and take appropriate follow-up actions, such as quarantine, phone surveillance, or self-monitoring. Contacts may also be referred to NCID for assessment.

Vaccination

There are currently no vaccines to prevent CCHF.

Notification

CCHF is an emerging infectious disease and is legally notifiable in Singapore. All suspected cases of CCHF should be reported to CDA immediately and instructions will be provided on further management of these cases. CDA will arrange for transfer of suspected cases to the NCID on a case-by-case basis. All confirmed cases will be managed at the HLIU in NCID.

Who should notify:

• Medical practitioners

• Laboratories

When to notify:

• On clinical suspicion

• On laboratory confirmation

How to notify:

• Please refer to the Infectious Disease Notification (opens in new tab) for more information.

Notification timeline:

• Immediately

Resources

Get more information on CCHF from the World Health Organisation (WHO). (opens in new tab)